Serious Mental Illness

Annotated Abstracts of Journal Articles
2014, 4th Quarter

Serious Mental Illness

Annotations by Lydia Chwastiak, MD, MPH, FAPM and Oliver Freudenreich, MD, FAPM
December 2014

  1. Management of new hyperglycemia in patients prescribed antipsychotics
  2. The STRIDE weight loss and lifestyle intervention for individuals taking antipsychotic medications: A randomized trial
  3. Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study

Also of interest:

  • Williams JM, Stroup TS, Brunette MF, Raney LE: Tobacco use and mental illness: A wake-up call for psychiatrists
    Psychiatr Serv 2014; 65(12):1406-8 ["Integrated Care" column]

    This regular column in Psychiatric Services on integrated care focuses on service delivery and policy issues at the medical-psychiatric interface. The December 2014 column highlights the unchanging, very high prevalence of tobacco use among community mental health patients and its negative health impact, and calls on psychiatrists to assume a leadership role in treatment of tobacco use disorders in this population.


PUBLICATION #1 — Serious Mental Illness
Management of new hyperglycemia in patients prescribed antipsychotics

Viverito K, Owen R, Mittal D, Li C, Williams JS
Psychiatr Serv 2014; 65(12):1502-5

ANNOTATION (Chwastiak & Freudenreich)

The Finding: This retrospective cohort analysis included more than 50,000 veterans who were receiving treatment with antipsychotic medication in 32 VA facilities in western states. Of the 33,403 patients who received a new antipsychotic prescription and did not have impaired glucose tolerance in the past year, 19,290 had a glucose or Hemoglobin A1c test within 180 days of the index prescription. 403 of these patients had evidence of clinically significant hyperglycemia. For these patients, only 63% received any intervention to address this hyperglycemia, typically a primary care visit. Nutrition counselling and referral to evidence-based lifestyle programs appeared to be under-utilized.

Strength and Weaknesses: The strengths of the study include the setting of the national (regional) VA. As this is a large integrated healthcare system, pharmacy, lab and visit data (including to an evidence-based lifestyle modification program) were available for analysis.

    The limitations of the study are the relatively small sample size (400) and the use of administrative data to specify clinical decision making and activities. The evaluation of the barriers to intervention was beyond the scope of these analyses.

Relevance: This is the first study to examine the extent to which patients who develop metabolic side effects from antipsychotic medications receive specific management for these adverse effects. It suggests that little intervention is provided in most cases and that a substantial percentage of patients receive no intervention at all.


Objective: This study examined the extent to which patients found to have clinically significant hyperglycemia after beginning a new antipsychotic receive guideline concordant management.

Methods: This retrospective cohort analysis (N=403) used U.S. Department of Veterans Affairs databases and multivariable logistic regression models to examine the association of patient characteristics with the likelihood of receiving recommended management.

Results: Overall, 63% of patients (N=254) received at least one type of management action within 30 days of identification of hyperglycemia. A primary care encounter was the most common action. Weight management program encounter, nutrition encounter, diabetes clinic encounter, and change in antipsychotic medications were underutilized interventions. Counseling related to weight management, nutrition, and diabetes that occurred during other visits with providers was not measured. Older patients and female patients were less likely to receive timely management. Preexisting comorbidities inconsistently influenced management practices.

Conclusions: Timely hyperglycemia management actions were not recorded in administrative data for a sizable minority of patients. Further research is needed to determine the full extent of appropriate management actions in this context.

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PUBLICATION #2 — Serious Mental Illness
The STRIDE weight loss and lifestyle intervention for individuals taking antipsychotic medications: A randomized trial
Green CA, Yarborough BJ, Leo MC
Am J Psychiatry 2015; 172(1):71-81

ANNOTATION (Chwastiak & Freudenreich)

The Finding: In this large, multi-site RCT in community settings and an integrated health plan, a 6-month weekly group lifestyle modification intervention led to weight loss and improved fasting glucose levels among individuals with a BMI >27 who were taking antipsychotic medications (compared to usual care). Mean weight loss was 4.4 kg among the intervention participants at 6 months.

Strength and Weaknesses: This was a large (n= 144), rigorously conducted randomized controlled trial. The study intervention is evidence-based, and is manualized, which supports evaluation of fidelity and increases the possibility for dissemination.

    Limitations include limited reach of the intervention, especially among certain vulnerable subgroups (racial and ethnic minorities). Severity of medical illness / medical complexity was not evaluated as this data was unavailable, and so groups could not be compared with respect to this covariate.

Relevance: This intervention appears much more feasible than previous lifestyle modification interventions for patients with serious mental illness. The ACHIEVE trial was conducted in psychiatric rehabilitation centers and involved daily programs that capitalized on client presence for several hours daily. STRIDE, in contrast, was a weekly group. This greatly increases the likelihood of implementation in real-world settings. This is also the first study to demonstrate a significant impact of a lifestyle modification intervention on fasting glucose for this population.


Objectives: The STRIDE study assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism.

Method: The study design was a multisite, parallel two-arm randomized controlled trial in community settings and an integrated health plan. Participants who met inclusion criteria were ≥18 years old, were taking antipsychotic agents for ≥30 days, and had a body mass index ≥27. Exclusions were significant cognitive impairment, pregnancy/breastfeeding, recent psychiatric hospitalization, bariatric surgery, cancer, heart attack, or stroke. The intervention emphasized moderate caloric reduction, the DASH (Dietary Approaches to Stop Hypertension) diet, and physical activity. Blinded staff collected data at baseline, 6 months, and 12 months.

Results: Participants (men, N=56; women, N=144; mean age=47.2 years [SD=10.6]) were randomly assigned to usual care (N=96) or a 6-month weekly group intervention plus six monthly maintenance sessions (N=104). A total of 181 participants (90.5%) completed 6-month assessments, and 170 (85%) completed 12-month assessments, without differential attrition. Participants attended 14.5 of 24 sessions over 6 months. Intent-to-treat analyses revealed that intervention participants lost 4.4 kg more than control participants from baseline to 6 months (95% CI=-6.96 kg to -1.78 kg) and 2.6 kg more than control participants from baseline to 12 months (95% CI=-5.14 kg to -0.07 kg). At 12 months, fasting glucose levels in the control group had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in the intervention group from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study-related; medical hospitalizations were reduced in the intervention group (6.7%) compared with the control group (18.8%).

Conclusions: Individuals taking antipsychotic medications can lose weight and improve fasting glucose levels. Increasing reach of the intervention is an important future step.

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PUBLICATION #3 — Serious Mental Illness
Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study
Correll CU, Robinson DG, Schooler NR, et al
JAMA Psychiatry 2014; 71(12):1350-63

ANNOTATION (Chwastiak & Freudenreich)

The Finding: This paper reports baseline data about cardiometabolic risk factors among young patients presenting with a first episode of schizophrenia. Data are from the NIMH-funded RAISE-ETP study, which is a cluster-randomized comparison of an integrated program of medication treatment, a decision support system, individual psychotherapy, family psychoeducation, and supported employment vs community care (determined by the clinician’s or patient’s choice).

Strength and Weaknesses: The sample is large and representative of the first-episode population, so these findings are quite generalizable. RAISE study sites included 34 community mental health centers without major research, teaching, or clinical first-episode programs, located in diverse communities.

    There are several limitations of this study, most relating to difficulty attributing cause of metabolic disorders to the use of specific medications. Only 50 participants were antipsychotic naïve, and data on the exact history of type and sequence of antipsychotic treatment prior to the baseline antipsychotic were not complete enough to allow analyses. Also, multiple analyses without adjustment for multiple testing limit the ability to assign causality to differences in cardiometabolic risk between medication groups. Diet and exercise were not assessed. Finally, numbers of patients representing racial and ethnic groups other than white and black were small, limiting the generalizability of the findings to these groups.

Relevance: Significant cardiometabolic risk is already present among young patients presenting with a first episode of schizophrenia (mean age in this study was 26). Prevention and early intervention to reduce metabolic risk are critical for this population.


Importance:  The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear.

Objective: To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity.

Design, Setting, and Participants:  Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment.

Exposure: Prebaseline antipsychotic treatment was based on the community clinician’s and/or patient’s decision.

Main Outcomes and Measures: Body composition and fasting lipid, glucose, and insulin parameters.

Results:  In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P ≤ .01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P ≤ .02).

Conclusions and Relevance: In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.

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